Project Summary/Abstract This proposal seeks funds to purchase the Perkin Elmer Opera Phenix High Content Screening System, an automated high throughput confocal microscope that is capable of simultaneously acquiring multicolor confocal images at unparalleled speed and sensitivity. There is a strong and growing research demand for high throughput and high content imaging of microtissues such as organoids or tumor spheroids and HT screening for small molecule, shRNA and CRISPR libraries to identify specific perturbants to achieve better understanding of the biological processes in our close knit research community. The Opera Phenix is a fully integrated and state-of-art imaging system that uses brightfield, wide-field and microlens enhanced spinning disk confocal optics to acquire images from a variety of types of biological samples on microtiter plates (6, 12, 24, 96, 384 and 1536 well) or microscope slides. The requested instrument system will benefit many NIH- funded investigators at the University of Colorado-Boulder. The capabilities of imaging bacteria, stress granules, subcellular organelle structures and mitochondria in a high throughput manner will greatly accelerate many ongoing research projects on our campus. Applications with automated HTS/HCS confocal microscopy is still being actively developed. We have a confluence of investigators who are devoted to the advancement of imaging solutions for biological systems. With availability of a shared automated HTS/HCS confocal microscope, this group of investigators will push the boundaries for this emerging technology. Funding of the requested PE Opera Phenix at CU-Boulder would facilitate the discovery of novel targets for diseases, bioprobes for biological studies, molecular design, protein analysis and specific targets associated in therapeutic applications. The centralized use of the instrument in the core facility will facilitate adoption of this technology across many disciplines of study and maximize use of the complementary shared resources at CU-Boulder.